What is tripolidine?

Triprolidine: A First-Generation Antihistamine

Triprolidine is a first-generation antihistamine primarily used for allergic rhinitis that causes significant sedation and anticholinergic effects, making it potentially inappropriate for older adults due to its side effect profile. 1

Pharmacological Classification and Properties

• Triprolidine is classified as a first-generation antihistamine that works by blocking H1 receptors 1
• It is available in oral formulations, with the FDA-approved form containing 0.938mg of triprolidine hydrochloride per 1 mL as an antihistamine 2
• Triprolidine has a relatively short half-life of approximately 2.1 ± 0.8 hours compared to other first-generation antihistamines 3
• Peak serum concentration occurs about 2 hours after ingestion, with a mean peak concentration of 15.4 ± 8.3 ng/ml 3
• Only about 1.3% of the drug is excreted unchanged in urine over 24 hours 3

Clinical Uses

• Primarily used for the symptomatic treatment of allergic rhinitis, particularly for reducing sneezing and eye irritation 4
• Standard dosing for adults ranges from 1.25 mg to 2.5 mg three times daily for allergic rhinitis 4
• Has been studied for temporary sleep disturbance due to its sedative properties, with doses of 2.5 mg showing improvement in sleep quality 5
• Often combined with decongestants like pseudoephedrine for treatment of infectious, allergic, and vasomotor rhinitis 6

Efficacy

• Triprolidine 2.5 mg three times daily has been shown to be statistically significantly better than placebo in reducing symptoms of sneezing and eye irritation in allergic rhinitis 4
• Produces dose-related antagonism of both flare and weal responses to histamine, with maximal effect at 3 hours after administration 7
• Suppression of histamine-induced flare has been documented at 2,3,6, and 8 hours after administration 3
• When used for sleep disturbance, triprolidine 2.5 mg demonstrated improvements in both objective and subjective measures of sleep quality compared to placebo 5

Side Effects and Safety Concerns

• Significant sedation and cognitive impairment are major concerns with triprolidine use 1
• Auditory vigilance is significantly impaired 1-2 hours after administration of all doses (1.25 mg, 2.5 mg, and 5 mg) 7
• Reaction time is prolonged in a dose-related manner at 2.5 and 5 hours after administration 7
• First-generation antihistamines like triprolidine have anticholinergic effects that may explain their better control of rhinorrhea compared to second-generation antihistamines 1
• Considered potentially inappropriate for older adults due to anticholinergic effects that can worsen conditions such as prostatic hypertrophy, elevated intraocular pressure, and cognitive impairment 1

Special Populations

• Triprolidine is classified as a medication with moderate evidence and strong recommendation to avoid in older adults according to updated practice parameters 1
• In children, it has been used at adjusted doses for allergic rhinitis, but caution is warranted due to sedative effects 6
• Patients with pre-existing conditions such as prostatic hypertrophy, elevated intraocular pressure, or cognitive impairment are at high risk for side effects 1

Comparison to Other Antihistamines

• Unlike second-generation antihistamines, triprolidine causes significant central nervous system effects including drowsiness and impaired performance 1, 7
• Compared to clemastine (another antihistamine), triprolidine produces earlier onset of sedation (1-2 hours) while clemastine's sedative effects peak later (5-6 hours) 7
• Triprolidine has a shorter duration of action compared to many other first-generation antihistamines, which may be advantageous in certain clinical scenarios 3, 5

Clinical Recommendations

• Second-generation antihistamines are generally preferred over first-generation agents like triprolidine due to their improved safety profile and reduced sedation 1
• When using triprolidine, patients should be warned about potential sedation and advised against driving or operating machinery 7
• The optimal dose for allergic rhinitis appears to be 2.5 mg three times daily, while 2.5 mg appears optimal for temporary sleep disturbance 4, 5
• Tolerance to the sedative effects may develop after continued use, with studies showing reduced drowsiness during the second week of treatment 4